Research Article Details
| Article ID: | A49751 |
| PMID: | 35647758 |
| Source: | J Clin Endocrinol Metab |
| Title: | Normal HDL cholesterol efflux and anti-inflammatory capacities in type 2 diabetes despite lipidomic abnormalities. |
| Abstract: | OBJECTIVE: To assess whether, in type 2 diabetic (T2D) patients, lipidomic abnormalities in high density lipoproteins (HDL) are associated with impaired cholesterol efflux capacity and anti-inflammatory effect, two pro-atherogenic abnormalities. DESIGN AND METHODS: This is a secondary analysis of the Lira-NAFLD study, including 20 T2D patients at T0 and 25 control subjects. Using liquid chromatography/tandem mass spectrometry, we quantified 110 species of the main HDL phospholipids and sphingolipids. Cholesterol efflux capacity was measured on THP-1 macrophages. The anti-inflammatory effect of HDL was measured as their ability to inhibit the TNFα-induced expression of Vascular Cell Adhesion Molecule-1 (VCAM-1) and Intercellular Cell Adhesion Molecule-1 (ICAM-1) on Human Vascular Endothelial Cells (HUVEC). RESULTS: The cholesterol-to-triglyceride ratio was decreased in HDL from T2D patients compared to controls (-46%, P=0.00008). As expressed relative to apolipoprotein AI, the amounts of phosphatidylcholines, sphingomyelins and sphingosine-1-phosphate were similar in HDL from T2D patients and controls. Phosphatidylethanolamine-based plasmalogens and ceramides were respectively 27% (P=0.038) and 24% (P=0.053) lower in HDL from T2D patients than in HDL from controls, whereas phosphatidylethanolamines were 41% higher (P=0.026). Cholesterol efflux capacity of apoB-depleted plasma was similar in T2D patients and controls (36.2±4.3 vs 35.5±2.8%, P=0.59). The ability of HDL to inhibit the TNFα-induced expression of both VCAM-1 and ICAM-1 at the surface of HUVEC was similar in T2D patients and controls (-70.6±16.5 vs -63.5±18.7%, P=0.14 and -62.1±13.2 vs -54.7±17.7%, P=0.16, respectively). CONCLUSION: Despite lipidomic abnormalities, the cholesterol efflux and anti-inflammatory capacities of HDL are preserved in T2D patients. |
| DOI: | 10.1210/clinem/dgac339 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S05 | Anti-inflammatory | inflammatory | Bile acid; TNF-a inhibitor; Dual PPAR-α and -δ agonists; Toll-Like Receptor; (TLR)-4 antagonist; Caspase inhibitor; ASK-1 inhibitor | Ursodeoxycholic Acid; Pentoxifylline; Elafibranor; JKB-121; Emricasan; Selonsertib; | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I05 | 9352 | Type 2 diabetes mellitus | A diabetes that is characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both. A diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. http://en.wikipedia.org/wiki/Diabetes, http://en.wikipedia.org/wiki/Diabetes_mellitus_type_2 | disease of metabolism/inherited metabolic disorder/ carbohydrate metabolic disorder/glucose metabolism disease/diabetes/ diabetes mellitus | Details |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D258 | Omega 3 PUFA | Chemical drug | DB11133 | PPARG ligand; PPARA activator | Hypolipidemic drug | Under clinical trials | Details |
| D328 | Serine | Chemical drug | DB00133 | SRR | Improve insulin resistance | Under clinical trials | Details |
| D075 | Choline | Supplement | DB00122 | PLD2 product of; PLD1 product of | -- | Under clinical trials | Details |
| D080 | Citrulline | Chemical drug | DB00155 | -- | -- | Under clinical trials | Details |
| D273 | Phosphatidylcholine | Chemical drug | DB15834 | -- | -- | Under clinical trials | Details |
| D125 | Epanova | Chemical drug | DB11133 | PPARG ligand; PPARA activator | Enhance lipid metabolism | Under clinical trials | Details |
| D094 | Cysteamine | Chemical drug | DB00847 | GSS stimulant | Renal drug | Under clinical trials | Details |
| D095 | Cysteamine bitartrate | Chemical drug | DB00847 | -- | -- | Under clinical trials | Details |